Ulcerative Colitis (UC)
Phase 3 Study of Ponesimod for Moderately to Severely Active Ulcerative Colitis
This study is investigating the efficacy and safety of oral ponesimod compared with placebo in adults with moderately to severely active ulcerative colitis.
Registry title: Study to Evaluate the Efficacy and Safety of Ponesimod (VSP-128) in Patients With Moderately to Severely Active Ulcerative Colitis
2 recruiting U.S. sites ↓Study at a glance
- Age
- 18 Years–75 Years
- Treatment
- Ponesimod or Placebo
- Design
- Randomized · Quadruple
- Central study contact
- Vanda Pharmaceuticals Inc.202-734-3400clinicaltrials@vandapharma.com
- Sponsor
- Vanda Pharmaceuticals
Research question
Does ponesimod improve ulcerative colitis outcomes at Week 16, and what safety findings occur, compared with placebo in this study population?
Participant snapshot
Who the study is looking for
- The study is looking for adults ages 18 through 75.
- The study is looking for people diagnosed with ulcerative colitis at least 90 days before screening.
- The study is looking for people whose ulcerative colitis meets the specified Mayo, endoscopy, and rectal-bleeding activity thresholds.
- The study is looking for people with an inadequate response, loss of response, or intolerance to at least one approved ulcerative colitis therapy.
Participation overview
What participation may involve
Participants take ponesimod or matching placebo by mouth once daily for 16 weeks. Those who enter the optional open-label extension receive ponesimod for 36 additional weeks. What participation may involve: - Take assigned ponesimod or matching placebo by mouth once daily during the 16-week double-blind period. - Follow a 14-day ponesimod titration or matching mock titration before continuing the assigned daily dose. - Undergo assessment of clinical remission, clinical response, Mayo Score, endoscopic improvement, and symptomatic remission at Week 16. - Participants may enter a 36-week open-label extension in which everyone receives ponesimod. The double-blind treatment period lasts 16 weeks, and participants may enter a 36-week open-label extension.
Study interventions
What participants may receive or do
- Ponesimod: Ponesimod is taken by mouth once daily. Treatment begins with a 14-day titration, followed by a stable daily dose from Day 15 through the end of treatment. Participants may then enter a 36-week open-label extension receiving ponesimod.
- Placebo: A matching placebo is taken by mouth once daily during the 16-week double-blind period. It uses a mock 14-day titration to maintain blinding. Participants may then enter a 36-week open-label extension receiving ponesimod.
Study design
How the comparison works
This Phase 3 treatment study assigns participants in parallel to ponesimod or matching placebo for a 16-week double-blind period, followed by an optional 36-week open-label ponesimod extension. Participants are randomly assigned in a 2:1 ratio to ponesimod or placebo during the 16-week double-blind period. Participants, care providers, investigators, and outcome assessors are masked to treatment assignment during the double-blind period. The control group receives matching placebo once daily, including a mock titration intended to preserve blinding. The reported 2:1 assignment ratio means two participants are assigned to ponesimod for every one assigned to placebo during the double-blind period.
Reported activities
Procedures and tests
- Screening must confirm a three-component Mayo score of 5 to 9, an endoscopy subscore of at least 2, and a rectal-bleeding subscore of at least 1.
- Clinical remission is assessed at Week 16.
- Clinical response and symptomatic remission are assessed at Week 16.
- The three-component Mayo Score is assessed at baseline and Week 16.
- Endoscopic improvement is assessed at Week 16.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Participants must be 18 through 75 years old.
- Participants must be able to provide written informed consent.
- Ulcerative colitis must have been diagnosed at least 90 days before screening.
- Disease activity must include a three-component Mayo score of 5 to 9, endoscopy subscore of at least 2, and rectal-bleeding subscore of at least 1.
- Participants must have had an inadequate response, loss of response, or intolerance to at least one approved ulcerative colitis therapy.
Possible reasons someone may not be able to join
- People with severe or fulminant ulcerative colitis likely to require hospitalization or surgery are excluded.
- People diagnosed with Crohn's disease or another type of colitis other than ulcerative colitis are excluded.
- Previous exposure to a sphingosine-1-phosphate receptor modulator is not allowed.
- People with active or chronic infections are excluded.
- Clinically significant cardiovascular or liver disease, or another uncontrolled systemic disease, is exclusionary.
- A history of an allergic reaction or significant sensitivity to study-drug ingredients is exclusionary.
Important unknowns
What the record does not make clear
- The registry does not state how many in-person or remote visits are required or when they occur.
- The registry does not state which current ulcerative colitis treatments may continue during the study.
- The registry does not report whether medications must be stopped for a specified period before treatment begins.
- The registry does not describe permitted rescue treatment if ulcerative colitis worsens.
- The record requires an endoscopy subscore for screening and evaluates endoscopic improvement at Week 16, but it does not describe the exact procedures, preparation, or additional endoscopies.
- The registry does not explain which study-related or routine-care costs are covered or billed to insurance.
- The registry does not state whether participants receive compensation.
- The registry does not state whether mileage, lodging, parking, or other travel expenses are reimbursed.
- The registry does not state whether any visits or assessments can be completed remotely.
- The record describes an optional 36-week open-label ponesimod extension but does not describe access after that extension ends.
Before contacting the site
Questions for the study team
- What is the full schedule and expected length of screening, treatment, extension, and follow-up visits?
- Which current ulcerative colitis medicines can continue, and are any washout periods required?
- What happens if ulcerative colitis symptoms worsen during the placebo-controlled period?
- What endoscopies are required, and what preparation, sedation, and recovery time do they involve?
- Which study-related costs are covered, and are compensation or travel reimbursements available?
- What additional eligibility checks are required beyond the criteria listed in the registry?
- What happens after the optional 36-week open-label extension ends?
Before changing care
Questions for your gastroenterologist
- How might the study's medication rules affect the continuity of my current ulcerative colitis treatment?
- How stable is my ulcerative colitis now, and what concerns would you have about a 16-week placebo-controlled period?
- What approved treatment alternatives should I compare with this study before making any decision?
- Are there cardiovascular, liver, infection, allergy, or medication-history concerns that I should discuss with the research team?
- How should you and the research team coordinate monitoring and care if my symptoms change?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
A multicenter, randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of Ponesimod (VSP-128) in patients with moderately to severely active ulcerative colitis
Study design and administration
- Organization
- Vanda Pharmaceuticals
- Organization class
- Industry
- Organization study ID
- VP-VSP-128-3201
- Lead sponsor
- Vanda Pharmaceuticals
- Sponsor class
- Industry
- Enrollment type
- Estimated
- Allocation
- Randomized
- Intervention model
- Parallel
- Primary purpose
- Treatment
- Masking
- Quadruple
- Who is masked
- Participant, Care Provider, Investigator, Outcomes Assessor
- Standard age groups
- Adult, Older Adult
Study arms
Experimental
Ponesimod (VSP-128)
Interventions: Drug: Ponesimod
Placebo Comparator
Placebo
Interventions: Drug: Placebo
Interventions
Drug
Ponesimod
Ponesimod administered orally once daily. Participants are randomized 2:1 to Ponesimod or placebo during a 16-week double-blind period. A 14-day titration is followed by a stable dose daily from Day 15 through end of treatment. Participants may enter a 36-week open-label extension receiving Ponesimod.
Drug
Placebo
Matching placebo administered orally once daily during a 16-week double-blind period (2:1 randomization). A mock 14-day titration is used to maintain blinding. Participants may enter a 36-week open-label extension receiving Ponesimod.
Eligibility
18 Years–75 Years
All
Not accepted
Inclusion criteria (5)
- Male and female subjects aged 18-75 yearsRegistry-derived · unreviewed
- Able to provide written informed consentRegistry-derived · unreviewed
- Diagnosis of ulcerative colitis for ≥90 days prior to screeningRegistry-derived · unreviewed
- Three-component Mayo score of 5-9 with endoscopy subscore ≥2 and rectal bleeding subscore ≥1Registry-derived · unreviewed
- History of inadequate response, loss of response, or intolerance to at least one approved UC therapyRegistry-derived · unreviewed
Exclusion criteria (6)
- Severe or fulminant UC likely to require hospitalization or surgeryRegistry-derived · unreviewed
- Diagnosis of Crohn's disease or other non-UC colitisRegistry-derived · unreviewed
- Prior exposure to S1P receptor modulatorsRegistry-derived · unreviewed
- Active or chronic infectionsRegistry-derived · unreviewed
- Clinically significant cardiovascular, hepatic, or other uncontrolled systemic diseaseRegistry-derived · unreviewed
- History of an allergic reaction or significant sensitivity to constituents of study drugRegistry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Clinical Remission at Week 16
Time frame: Week 16
Proportion of participants achieving clinical remission at Week 16.
Secondary outcome
Clinical Response at Week 16
Time frame: Week 16
Proportion of participants achieving clinical response at Week 16.
Secondary outcome
Change From Baseline in Mayo Score at Week 16
Time frame: Baseline to Week 16.
Change from baseline in the three-component Mayo Score at Week 16. The overall score value ranges from 0 to 9, with higher scores indicating more severe ulcerative colitis disease activity.
Secondary outcome
Endoscopic Improvement at Week 16
Time frame: Week 16
Proportion of participants achieving endoscopic improvement at Week 16.
Secondary outcome
Symptomatic Remission at Week 16
Time frame: Week 16
Proportion of participants achieving symptomatic remission at Week 16.
Recruiting locations in the United States
Vanda Investigational Site
RecruitingChula Vista, California, 91910, United States
Vanda Investigational Site
RecruitingNashville, Tennessee, 37211, United States
Central study contacts
Registry dates
- First posted
- Jul 7, 2026
- Primary completion
- Apr 2029
- Overall completion
- Aug 2029
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.